The value of screening biopsies in light-chain (AL) and transthyretin (ATTR) amyloidosis.
Oliver C Cohen, Faye Sharpley, Janet A Gilbertson, Ashutosh D Wechalekar, Sajitha Sachchithanantham, Shameem Mahmood, Carol J Whelan, Ana Martinez-Naharro, Marianna Fontana, Helen J Lachmann, Philip N Hawkins, Julian D Gillmore
Author Information
Oliver C Cohen: National Amyloidosis Centre, Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine, University College London, London, UK. ORCID
Faye Sharpley: National Amyloidosis Centre, Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine, University College London, London, UK.
Janet A Gilbertson: National Amyloidosis Centre, Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine, University College London, London, UK.
Ashutosh D Wechalekar: National Amyloidosis Centre, Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine, University College London, London, UK.
Sajitha Sachchithanantham: National Amyloidosis Centre, Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine, University College London, London, UK.
Shameem Mahmood: National Amyloidosis Centre, Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine, University College London, London, UK.
Carol J Whelan: National Amyloidosis Centre, Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine, University College London, London, UK.
Ana Martinez-Naharro: National Amyloidosis Centre, Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine, University College London, London, UK.
Marianna Fontana: National Amyloidosis Centre, Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine, University College London, London, UK.
Helen J Lachmann: National Amyloidosis Centre, Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine, University College London, London, UK.
Philip N Hawkins: National Amyloidosis Centre, Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine, University College London, London, UK.
Julian D Gillmore: National Amyloidosis Centre, Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine, University College London, London, UK.
INTRODUCTION: Systemic amyloidosis is a histological diagnosis, often achieved via critical organ biopsy. Screening biopsies represent a low-risk approach to diagnosis. OBJECTIVES AND METHODS: All patients with systemic AL and ATTR amyloidosis who underwent abdominal fat aspiration (AFA) and either a bone marrow (BM) or gastrointestinal (GI) biopsy at the UK National amyloidosis Centre (2006-2019) were identified. We sought to determine diagnostic sensitivity in relation to whole body amyloid burden, amyloid type and organ involvement. RESULTS: Diagnostic sensitivity established in 471 patients with AL (n = 321) and ATTR (n = 150) amyloidosis, respectively, was 73.2% and 27.3% for AFA (P< .001), 59.7% and 42.2% for BM (P< .001), and 74.6% and 44.6% for GI biopsy (P< .001). ATTR amyloid deposits were detected in 35.4% BMs and 33.3% of GI biopsies when AFA did not demonstrate amyloid. In ALamyloidosis, sensitivity of combined AFA and BM biopsy in ALamyloidosis was 82.9%. There was a strong association between whole body amyloid burden and sensitivity of each screening biopsy method. The diagnostic sensitivity of screening biopsies ranged from 80.0% to 90.5% for patients with a large amyloid load on I-SAP scintigraphy in comparison with 53.9%-79.0% in those with no visceral amyloid visible on imaging. CONCLUSION: Performing both AFA and BM biopsy should be considered in suspected ALamyloidosis to substantially reduce the clinical risk associated with critical organ biopsy. The sensitivity of screening biopsies in ATTR amyloidosis is poor.
Vaxman I, Gertz M. Recent advances in the diagnosis, risk stratification, and management of systemic light-chain amyloidosis. Acta Haematol. 2019;141(2):93-106.
Li T, Huang X, Cheng S, et al. Utility of abdominal skin plus subcutaneous fat and rectal mucosal biopsy in the diagnosis of AL amyloidosis with renal involvement. PLoS One. 2017;12(9):e0185078.
Gillmore JD, Wechalekar A, Bird J, et al. Guidelines on the diagnosis and investigation of AL amyloidosis. Br J Haematol. 2015;168(2):207-218.
Maurer MS. Noninvasive Identification of ATTRwt cardiac amyloid: the re-emergence of nuclear cardiology. Am J Med. 2015;128(12):1275-1280.
Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133(24):2404-2412.
Westermark P, Stenkvist B. A new method for the diagnosis of systemic amyloidosis. Arch Intern Med. 1973;132(4):522-523.
Kimmich C, Schonland S, Kraker S, et al. Amyloid in bone marrow smears in systemic light-chain amyloidosis. Amyloid. 2017;24(1):52-59.
Quarta CC, Gonzalez-Lopez E, Gilbertson JA, et al. Diagnostic sensitivity of abdominal fat aspiration in cardiac amyloidosis. Eur Heart J. 2017;38(24):1905-1908.
Vrana JA, Theis JD, Dasari S, et al. Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics. Haematologica. 2014;99(7):1239-1247.
Fernandez de Larrea C, Verga L, Morbini P, et al. A practical approach to the diagnosis of systemic amyloidoses. Blood. 2015;125(14):2239-2244.
Muchtar E, Dispenzieri A, Lacy MQ, et al. Overuse of organ biopsies in immunoglobulin light chain amyloidosis (AL): the consequence of failure of early recognition. Ann Med. 2017;49(7):545-551.
Staron A, Connors LH, Ruberg FL, Mendelson LM, Sanchorawala V. A new era of amyloidosis: the trends at a major US referral centre. Amyloid. 2019;26(4):192-196.
Cowan AJ, Seldin DC, Skinner M, et al. Amyloid deposits in the bone marrow of patients with immunoglobulin light chain amyloidosis do not impact stem cell mobilization or engraftment. Biol Blood Marrow Transplant. 2012;18(12):1935-1938.
Shidham VB, Hunt B, Jardeh SS, Barboi AC, Devata S, Hari P. Performing and processing FNA of anterior fat pad for amyloid. J Vis Exp. 2010;44.1747.
Gertz MA, Comenzo R, Falk RH, et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International symposium on amyloid and amyloidosis, Tours, France, 18-22 April 2004. Am J Hematol. 2005;79(4):319-328.
Devata S, Hari P, Markelova N, Li R, Komorowski R, Shidham VB. Detection of amyloid in abdominal fat pad aspirates in early amyloidosis: Role of electron microscopy and Congo red stained cell block sections. Cytojournal. 2011;8:11.
Lovat LB, Persey MR, Madhoo S, Pepys MB, Hawkins PN. The liver in systemic amyloidosis: insights from 123I serum amyloid P component scintigraphy in 484 patients. Gut. 1998;42(5):727-734.
